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The Skinny On Weight Loss Drugs Siggi Ming, ARNP, NP-C Weight Loss Center of Oklahoma Objectives Learner will be able to identify pharmacological agents currently approved by the FDA for the treatment of obesity Learner will be able to identify indications for the use of pharmacological agents when treating overweight/obese patients Learner will be able to discuss the use of pharmacological agents in combination with behavior modification, nutrition, and use of supplements in the treatment of overweight/obesity Definition of Overweight/Obesity Overweight: BMI of 25.0 – 29.9 kg/m2 Obese: BMI of 30.0 – 39.9 kg/m2 Morbidly Obese: BMI of 40.0 kg/m2 and > When to Treat Any time comorbidities are present, i.e. DM II, hyperlipidemias, heart disease, GERD, hypertension, metabolic syndrome, sleep apnea, stress incontinence Any time the patient requests help with weight loss efforts How Is Overweight/Obesity Treated? Behavior Modification and Lifestyle Changes Nutritional Counseling Exercise Counseling Correcting Endocrine Imbalances Supplements Prescription Medications Pharmacologic Agents Orlistat The only FDA approved drug for long term use Lipase Inhibitor; inhibits absorption of dietary fat Minimal systemic absorption Tmax approx. 8 hrs Half life approx. 1-2 hrs Metabolism occurs mainly in GI wall Elimination via fecal route (97%) Orlistat Indications & Dosage Obesity Management Weight Loss Weight maintenance 120 mg po tid with or < 1 hr after fat containing meal Omit if meal is non-fat Orlistat Contraindications Hypersensitivity Chronic malabsorption syndromes Cholestasis Hx of calcium oxalate kidney stones Hx of Anorexia or bulimia Hx of organ transplant Orlistat Adverse Reactions Serious: Hypersensitivity (anaphylaxis) Angioedema Vitamin deficiencies (fat soluble vit) hepatotoxicity Orlistat Adverse Reactions Common: Oily spotting Flatulence with fecal discharge Fecal urgency and incontinence Fatty, oily stools Abdominal discomfort Orlistat Drug Interactions Warfarin: Watch for increased INR due to decreased Vitamin K absorption Cyclosporine: Decreased levels Amiodarone: Decreased levels Fat soluble vitamins (K, A, D, E): Decreased absorption Thyroid hormone: Decreased absorption Orlistat Safety Pregnancy Category B Lactation safety unknown Monitoring: no routine testing recommended Drugs approved for short term use Phentermine Diethylpropion Phendimetrazine Phentermine FDA approved for short term use (up to 12 weeks) Sympathomimetic; stimulates CNS activity; stimulates catecholamine release, thereby decreasing hunger Rapidly absorbed from GI tract Half life approx. 24 hrs Excretion: 70-80% unchanged in urine Phentermine Indications & Dosage Short term treatment of obesity 37.5 mg po qd before 1000 to avoid insomnia Start with ½ strength Increase dosage to full strength if ½ strength not causing enough appetite suppression Phentermine Contraindications Hypersensitivity MAOI use Arteriosclerosis Cardiovascular disease Hyperthyroidism Glaucoma Agitation Hx of drug abuse Pregnancy Breastfeeding Phentermine Adverse Reactions Serious: Dependency Psychosis Tachycardia Hypertension Pulmonary hypertension Valvular heart disease Phentermine Adverse Reactions Common: Palpitations Tachycardia Restlessness Insomnia Diarrhea Xerostomia Hypertension Euphoria Headache Phentermine Drug Interactions Anorexiants/stimulants (increased risk of CV, CNS stimulation) MAOIs (hypertensive crisis) Linezolid (increased risk for HTN) Effexor (additive effect) Phentermine Safety Pregnancy Category C Lactation: possibly unsafe CV evaluation at baseline (ECG, BP, physical CV exam; consider echo at baseline and after dc) Schedule IV Diethylpropion FDA approved for short term use (up to 12 weeks) Sympathomimetic; stimulates CNS activity; stimulates catecholamine release, thereby decreasing hunger Rapidly absorbed Half life 4-6 hrs Excretion: urine Diethylpropion Indications & Dosage Short term treatment of obesity 25 mg po up to tid; 75 mg ER qd 25 mg approx. 1 hr before “hungriest” time of day; may take up to tid Do not take after 1600 to avoid insomnia 75 mg ER q am Diethylpropion Contraindications Hypersensitivity Pulmonary hypertension Severe hypertension Agitation Valvular heart disease Heart murmur Cardiovascular disease Seizure disorder Advanced arteriosclerosis Diethylpropion Adverse Reactions Serious: Tachycardia Hypertension Pulmonary hypertension Valvular heart disease Hallucinations Psychosis Leukopenia Diethylpropion Adverse Reactions Common: Dry mouth Diarrhea/constipation Restlessness Anxiety Insomnia Headache Hypertension Palpitations Arrhythmias Diethylpropion Drug Interactions Anorexiants/stimulants (increased risk of CV and CNS stimulation MAOIs (hypertensive crisis) Linezolid (increased risk of HTN) Effexor (additive effects) Diethylpropion Safety Pregnancy Category B Lactation safety unknown Cardiovascular evaluation at baseline; ECG, BP, physical CV exam) Consider echo periodically and after dc Schedule IV Phendimetrazine FDA approved for short term use (up to 12 weeks) Sympathomimetic; stimulates CNS activity; stimulates catecholamine release, thereby decreasing hunger Rapidly absorbed Half life 2 hrs (10 hrs ER) Excretion: urine Phendimetrazine Indications & Dosage Short term treatment of obesity 17.5-35 mg po bid-tid; 1 hr ac Do not give after 1600 to avoid insomnia 105 mg ER po q am 30-60 mins ac Phendimetrazine Contraindications Hypersensitivity Symptomatic cardiovascular disease Moderate/severe hypertension Hyperthyroidism Agitation MAOI use Valvular heart disease Pregnancy Glaucoma Advanced arteriosclerosis Phendimetrazine Adverse Reactions Serious: Hypertension Tachycardia Pulmonary hypertension Withdrawal if abrupt dc after long term high-dose use Phendimetrazine Adverse Reactions Palpitations Tachycardia Restlessness Hypertension Insomnia Agitation Dizziness Headache Flushing Sweating Tolerance Diarrhea/constipation Common: Phendimetrazine Drug Interactions Anorexiants/stimulants (increased risk of CV and CNS stimulation MAOIs (hypertensive crisis) Linezolid (increased risk of HTN) Effexor (additive effects) Phendimetrazine Safety Pregnancy Category C Lactation possibly unsafe Cardiovascular evaluation at baseline; ECG, BP, physical CV exam Consider echo periodically and after dc Schedule III Drugs Used Off Label Pristiq Antidepressant (SNRI) Side effects include decreased appetite, weight loss Seems to decrease cravings Drugs Used Off Label Topamax For migraine/headache; seizure disorders Side effects include weight loss, anorexia Many undesirable side effects Drugs Used Off Label Spironolactone Decreases CHO cravings Useful prior to menses Start the day premenstrual S/S begin, stop when menstrual flow ceases Drugs Used Off Label Pindolol Weak beta blocker Use with phentermine, diethylpropion to block stimulant effect without affecting anorectic effect hCG Human chorionic gonadotropin Hormone secreted by the female body in response to pregnancy Used off and on since the 1950s in conjunction with a very low calorie diet (usually 500 kcal/day) hCG No evidence that hCG is associated with weight loss No evidence that the use of hCG is safe ASBP strongly discourages the use of hCG for weight loss Supplements Good quality supplements can aid weight loss efforts by - raising resting metabolic rate - increasing lipid metabolism - curbing hunger - raising energy levels Combined Effort Nutrition Behavior Lifestyle Medications/Supplements